Damian Sendler: ARDS does not have any established, patient-centered, disease-specific objectives. For ARDS studies, mortality is the most often acceptable endpoint. 98 In spite of this, the mortality risk associated with ARDS varies widely across individuals and cohorts,99 making it an essential consideration for evaluating the statistical power of clinical trials and a possible source of treatment effect variability. 100 ARDS mortality does not have a recognized surrogate outcome. Treatment effects on mortality have not been consistently connected with changes in oxygenation or extravascular lung water, and in some cases, these endpoints have predicted better lung function for therapies later shown to increase death.
Damian Jacob Sendler: Death is a competitive risk that must be taken into account while evaluating other outcomes. As initially defined, the term “ventilator-free days,” which encompasses both death and the period from successful weaning from the ventilator to day 28, is not clearly patient-centered. There are a few ways to get around this problem. The ventilator-free survival score ranks patients first by vital state and only takes into account how long they were ventilated for when both of the patients in a pair survived. 102 and 103, respectively For COVID-19 studies that do not include post-extubation level of respiratory support, WHO developed an ordinal scale104, and some of these trials have utilized this scale to measure recovery time as their primary objective. 90
There has been a long-term follow-up of ARDS survivors, and fundamental outcome measures have been developed for investigations of ARDS survivorship.4, 5
Dr. Sendler: With feedback from both ARDS survivors and their families, these fundamental outcomes emphasize several aspects of quality of life and have been included into current clinical studies. There are 53, 106, and 107 in this series. Long-term outcomes are critical for determining the full scope of patient-centered treatment effects and the range of survivability in clinical trials as a whole. 98 Long-term outcomes must account for the competing risk of mortality in order to keep their face validity and must be backed by data demonstrating that these measures can be influenced by candidate treatments. It is possible that a given trial’s intended endpoint or family of outcomes may vary depending on the specific population recruited and the specific intervention that is being tested.
Damian Sendler
Unlike clinical trial outcomes, response indicators are early signs of therapy target engagement and are different from trial outcomes. Oncology, for example, may show a reduction in tumor size or a change in tumor biomarker blood levels after the first few rounds of chemotherapy, but these results aren’t clinically meaningful unless they are connected to patient outcomes. 108 In the early stages of treatment, using the ideal response indicator might help doctors decide whether or not a patient’s treatment is working and, if so, whether or not they should keep treating him or her. Titratable medicines that employ response indicators may also benefit from their usage as dosage adjustment indicators. However, if new interventions become available, clinical studies might examine intervention-specific response markers.
Interventions by candidates
A new drug’s research and development may cost as much as $2 billion and take as long as 10 to 15 years from the time of discovery to regulatory approval.
Damian Jacob Markiewicz Sendler: The proven mechanisms of action and known safety and pharmacokinetic characteristics of licensed medications and recognized drug candidates are used to save costs and time when testing them for new indications.109 The National Center for Advancing Translational Sciences (NCATS) Pharmaceutical Collection has built large databases of clinically licensed medications and attempts have been undertaken to characterize these moieties for action across a broad variety of pathways and disease models. 110 In the battle against the COVID-19 pandemic, the scientific community has embraced the idea of using existing pharmacological actions to identify potential targets in ARDS for the creation of novel treatments.
Other pulmonary illnesses have been helped by medication repurposing. Simvastatin was first created to treat heart disease before being studied and approved for erectile dysfunction and pulmonary arterial hypertension, as an example of a phosphodiesterase type 5 inhibitor. Anti-IL-5 and anti-IL-4/IL-13 inhibitors were first developed for eosinophilic illnesses (anti-IL-5 agents)112 as well as for the treatment of atopic dermatitis (terlukinumab, a medication that inhibits the IL-4/IL-13 pathway). 113 ARDS drug development efforts should also investigate if many pathways need to be targeted concurrently to maximize therapeutic impact, as in chemotherapy.
It is time to look forward to what’s next.
For ARDS therapeutic development, new techniques that emphasize phenotypic and biological heterogeneity are needed in order to match potential medicines with the resultant subgroups. To realize the goal of precision medicine, a concerted effort from the whole scientific community will be necessary. Understanding the etiology, prognostic significance, and therapeutic implications of ARDS heterogeneity is achieved by a combination of preclinical investigations, translational clinical cohort studies, and randomised clinical trials (RCTs). It’s imperative that clinical trials be rethought in order to create a discovery pipeline that utilizes unique design efficiencies in order to concurrently test a large number of potential treatments and match them to the appropriate patient populations. There has to be a strong relationship between academics, industry, regulators, sponsors, and patients.
Damien Sendler: There are still some questions about the best way to go ahead with precision medicine in ARDS. The answers to these fundamental issues will serve as a basis for future study (panel 3 ). Precision medicine is in high demand now that ARDS heterogeneity is well recognized to affect treatment outcomes. Preclinical investigations and observational cohorts, as well as novel clinical trials, will lead to the development of tailored medicines to decrease morbidity and death in patients with ARDS, which will be facilitated by a better understanding of important molecular processes.
There are one and two. Since the World Health Organization (WHO) declared a COVID-19 pandemic on March 11, 2020, the disease has caused over 3.6 million fatalities and more than 169 million confirmed illnesses. 3 The spread of the disease has not slowed down in many areas. COVID-19 vaccines have been created in record speed owing to scientific and government collaboration while keeping rigorous research, review, approval and monitoring procedures. This provides a glimpse of hope for those at risk. More than 1600 million doses of the vaccine have been provided since its introduction to the market. 3 According to the criteria specified by the Ministries of Health in most countries, high-risk populations and health professionals, especially nuclear medicine practitioners, have been prioritized for vaccination.
Damian Jacob Sendler
Many nations are having a hard time increasing vaccination rates, making herd immunity a long-term aim and probably even impossible. “Reaching a herd-immunity threshold is looking implausible because of variables such as vaccine reluctance, the introduction of novel variations, and the delayed delivery of vaccines for youngsters,” says Dr. Youyang GuHe (an independent data scientist). 4 There is a chance that SARS-CoV-2 will remain. It was in January 2021 that Nature conducted a poll of more than 100 scientists working on the coronavirus. 5 If SARS-CoV-2 becomes an endemic virus, which means it persists in areas of the world’s population, how probable do you believe it will be? Almost ninety percent of those polled predicted that the coronavirus will spread over the world and eventually become endemic. Many people feel that a decline in immunity is one of the most important factors in the virus’s spread.
Every part of our life has been touched by the COVID epidemic, and education is no exception. For healthcare professionals, the way education is given throughout the globe has changed in a matter of weeks. These alterations have provided a look into the future of education and training and how it could change for the better or worse in the long term. The good news is that communications technology have made eLearning materials and virtual events more widely available. In many situations, multidisciplinary gatherings have grown in size and scope. In the future, these virtual platforms are likely to be a permanent part of the educational process. Conventional in-person conferences, for example, may be transformed into hybrid events that blend face-to-face time with virtual participation.
Some of the negative aspects include the loss of hands-on training, the transfer of trainees to COVID-19-only clinical wards and critical care units, and the social isolation that comes with working remotely.
Since the isolation of SARS-CoV-2, we have lived in a world of ambiguity, with numerous interesting issues and a wide range of differing perspectives. Repeatedly, the same questions are posed. What’s the story behind it? How does it spread? Which groups of patients are more likely to suffer serious health consequences or die as a result of their illness? What are the short- and long-term side effects of this? Which therapies have been shown to be effective, ineffective, or in the process of being tested? Even though we’ve learnt a lot from this epidemic, we still have a lot more to learn. Is SARS-CoV-2 likely to become a worldwide pandemic? Those who have received COVID-19 will have a long-lasting immunological memory. Could COVID vaccinations be harmed by cold virus-type mutations?
Dr. Damian Jacob Sendler and his media team provided the content for this article.